Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Originally published in Science Express on 7 January 2010
Science 12 February 2010:
Vol. 327. no. 5967, pp. 883 - 886
DOI: 10.1126/science.1183863
Prev | Table of Contents | Next

Reports

A Composite of Multiple Signals Distinguishes Causal Variants in Regions of Positive Selection

Sharon R. Grossman,1,2,*,{dagger} Ilya Shylakhter,1,2,*,{dagger} Elinor K. Karlsson,1,2 Elizabeth H. Byrne,1,2 Shannon Morales,1,2,3 Gabriel Frieden,1 Elizabeth Hostetter,1,2 Elaine Angelino,1,4 Manuel Garber,2 Or Zuk,2 Eric S. Lander,2,4,5 Stephen F. Schaffner,2 Pardis C. Sabeti1,2,4,{dagger}

The human genome contains hundreds of regions whose patterns of genetic variation indicate recent positive natural selection, yet for most the underlying gene and the advantageous mutation remain unknown. We developed a method, composite of multiple signals (CMS), that combines tests for multiple signals of selection and increases resolution by up to 100-fold. By applying CMS to candidate regions from the International Haplotype Map, we localized population-specific selective signals to 55 kilobases (median), identifying known and novel causal variants. CMS can not just identify individual loci but implicates precise variants selected by evolution.

1 Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
2 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
3 Mount Sinai School of Medicine, New York, NY 10029, USA.
4 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
5 Department of Biology, MIT, Cambridge, MA 02139, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: psabeti{at}oeb.harvard.edu (P.C.S.), shari.grossman{at}post.harvard.edu (S.R.G.), ilya_shl{at}alum.mit.edu (I.S.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Genetic Evidence for High-Altitude Adaptation in Tibet.
T. S. Simonson, Y. Yang, C. D. Huff, H. Yun, G. Qin, D. J. Witherspoon, Z. Bai, F. R. Lorenzo, J. Xing, L. B. Jorde, et al. (2010)
Science 329, 72-75
   Abstract »    Full Text »    PDF »
Colloquium Paper: Gene-culture coevolution in the age of genomics.
P. J. Richerson, R. Boyd, and J. Henrich (2010)
PNAS 107, 8985-8992
   Abstract »    Full Text »    PDF »
Measuring Natural Selection on Genotypes and Phenotypes in the Wild.
C. R. Linnen and H. E. Hoekstra (2010)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)